Antithrombotic thrombocytes: ectopic expression of urokinase-type plasminogen activator in platelets

Arterial occlusive disorders are a leading cause of human morbidity. We hypothesized that ectopic expression of fibrinolytic proteins in platelets could be used to favorably alter the hemostatic balance at sites of thrombosis. To test our hypothesis, we directed murine urokinase-type plasminogen act...

Descripción completa

Detalles Bibliográficos
Autores: Kufrin, Dubravka, Eslin, Donald, Bdeir, Khalil, Murciano, Juan Carlos, Kuo, Alice, Kowalska, M. Anna, Degen, Jay L., Sachais, Bruce S., Cines, Douglas B., Poncz, Mortimer
Tipo de recurso: artículo
Fecha de publicación:2003
País:España
Institución:Universidad Alfonso X el Sabio
Repositorio:Repositorio Institucional de la Universidad Alfonso X el Sabio
Idioma:inglés
OAI Identifier:oai:archive.uax.com:20.500.12080/45218
Acceso en línea:https://hdl.handle.net/20.500.12080/45218
Access Level:acceso abierto
id ES_7521c8f4e8200dbd9155f0bfc37bc838
oai_identifier_str oai:archive.uax.com:20.500.12080/45218
network_acronym_str ES
network_name_str España
repository_id_str
spelling Antithrombotic thrombocytes: ectopic expression of urokinase-type plasminogen activator in plateletsKufrin, DubravkaEslin, DonaldBdeir, KhalilMurciano, Juan CarlosKuo, AliceKowalska, M. AnnaDegen, Jay L.Sachais, Bruce S.Cines, Douglas B.Poncz, MortimerArterial occlusive disorders are a leading cause of human morbidity. We hypothesized that ectopic expression of fibrinolytic proteins in platelets could be used to favorably alter the hemostatic balance at sites of thrombosis. To test our hypothesis, we directed murine urokinase-type plasminogen activator transgene expression to platelets using a platelet factor 4 promoter. Urokinase was selectively expressed and stored in the platelets of these mice. These transgenic mice had altered platelet biology and a bleeding diathesis similar to that seen in patients with Quebec platelet disorder, affirming the role of ectopic urokinase expression as the etiology of this inherited disease. These mice were resistant to the development of occlusive carotid artery thrombosis in the absence of systemic fibrinolysis and displayed rapid resolution of pulmonary emboli. Moreover, transfusion of urokinase-expressing platelets into wild-type mice prevented formation of occlusive arterial thrombi. These studies show the feasibility of delivering fibrinolytic agents to sites of incipient thrombus formation through selective storage in platelets and offer a new strategy to prevent thrombosis and hemorrhage.UAX Archive20032003-08-0120032003-08-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.12080/45218reponame:Repositorio Institucional de la Universidad Alfonso X el Sabioinstname:Universidad Alfonso X el SabioInglésengopen accesshttp://purl.org/coar/access_right/c_abf2CC-BYhttp://creativecommons.org/licenses/by/4.0/deed.esinfo:eu-repo/semantics/openAccessoai:archive.uax.com:20.500.12080/452182026-05-28T12:40:21Z
dc.title.none.fl_str_mv Antithrombotic thrombocytes: ectopic expression of urokinase-type plasminogen activator in platelets
title Antithrombotic thrombocytes: ectopic expression of urokinase-type plasminogen activator in platelets
spellingShingle Antithrombotic thrombocytes: ectopic expression of urokinase-type plasminogen activator in platelets
Kufrin, Dubravka
title_short Antithrombotic thrombocytes: ectopic expression of urokinase-type plasminogen activator in platelets
title_full Antithrombotic thrombocytes: ectopic expression of urokinase-type plasminogen activator in platelets
title_fullStr Antithrombotic thrombocytes: ectopic expression of urokinase-type plasminogen activator in platelets
title_full_unstemmed Antithrombotic thrombocytes: ectopic expression of urokinase-type plasminogen activator in platelets
title_sort Antithrombotic thrombocytes: ectopic expression of urokinase-type plasminogen activator in platelets
dc.creator.none.fl_str_mv Kufrin, Dubravka
Eslin, Donald
Bdeir, Khalil
Murciano, Juan Carlos
Kuo, Alice
Kowalska, M. Anna
Degen, Jay L.
Sachais, Bruce S.
Cines, Douglas B.
Poncz, Mortimer
author Kufrin, Dubravka
author_facet Kufrin, Dubravka
Eslin, Donald
Bdeir, Khalil
Murciano, Juan Carlos
Kuo, Alice
Kowalska, M. Anna
Degen, Jay L.
Sachais, Bruce S.
Cines, Douglas B.
Poncz, Mortimer
author_role author
author2 Eslin, Donald
Bdeir, Khalil
Murciano, Juan Carlos
Kuo, Alice
Kowalska, M. Anna
Degen, Jay L.
Sachais, Bruce S.
Cines, Douglas B.
Poncz, Mortimer
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv UAX Archive
description Arterial occlusive disorders are a leading cause of human morbidity. We hypothesized that ectopic expression of fibrinolytic proteins in platelets could be used to favorably alter the hemostatic balance at sites of thrombosis. To test our hypothesis, we directed murine urokinase-type plasminogen activator transgene expression to platelets using a platelet factor 4 promoter. Urokinase was selectively expressed and stored in the platelets of these mice. These transgenic mice had altered platelet biology and a bleeding diathesis similar to that seen in patients with Quebec platelet disorder, affirming the role of ectopic urokinase expression as the etiology of this inherited disease. These mice were resistant to the development of occlusive carotid artery thrombosis in the absence of systemic fibrinolysis and displayed rapid resolution of pulmonary emboli. Moreover, transfusion of urokinase-expressing platelets into wild-type mice prevented formation of occlusive arterial thrombi. These studies show the feasibility of delivering fibrinolytic agents to sites of incipient thrombus formation through selective storage in platelets and offer a new strategy to prevent thrombosis and hemorrhage.
publishDate 2003
dc.date.none.fl_str_mv 2003
2003-08-01
2003
2003-08-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.12080/45218
url https://hdl.handle.net/20.500.12080/45218
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
CC-BY
http://creativecommons.org/licenses/by/4.0/deed.es
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
CC-BY
http://creativecommons.org/licenses/by/4.0/deed.es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositorio Institucional de la Universidad Alfonso X el Sabio
instname:Universidad Alfonso X el Sabio
instname_str Universidad Alfonso X el Sabio
reponame_str Repositorio Institucional de la Universidad Alfonso X el Sabio
collection Repositorio Institucional de la Universidad Alfonso X el Sabio
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869410958806351873
score 15.811543

Similares en LA Referencia